Hemorrhage and necrosis of the liver caused by hepatic arteriovenous malformations in a fetus: A case report

Rationale: Hepatic arteriovenous malformations (HAVMs) are a rare disorder reported in association with hereditary hemorrhagic telangiectasia (HHT), known as Rendu-Osler-Weber syndrome. HAVMs are usually detected in adulthood. Patient concerns: A 29-year-old pregnant woman underwent a routine prenatal examination at 37 weeks of pregnancy. Diagnosis and interventions: There were fetal liver anomalies detected by prenatal ultrasonography and were managed. Furthermore, a hepatic mass was detected and was subsequently analyzed by fetal magnetic resonance imaging. There were no typical imaging findings in this case which was once misdiagnosed as a hepatoblastoma. Outcomes: Considering the massive hepatic lesion, labor induction was performed on a pregnant woman to avoid adverse maternal and fetal outcomes. Histopathological examination confirmed the diagnosis of HAVMs. Lesions detected by imaging were determined to be hemorrhagic and necrotic. Lessons: Prenatal hepatic hemorrhage and necrosis due to an arteriovenous malformation are rare. The authors describe their observations and results.


Introduction
Hepatic arteriovenous malformations (HAVMs) are a rare disorder reported in association with hereditary hemorrhagic telangiectasia (HHT), known as Rendu-Osler-Weber syndrome. [1,2] This paper reports the first case of hemorrhage and necrosis of the liver caused by HAVMs, confirmed by histopathological examination in a fetus with complete imaging data.
Our case was presented with predominantly hemorrhage and necrosis caused by HAVMs that were not correctly diagnosed by ultrasonography and resonance imaging (MRI) imaging. Thus, this presentation aims to improve the understanding of this disease for sonographers and radiologists to better understand the prenatal diagnosis. Timely and correct diagnosis would allow better prenatal counseling and management decisions.

Case report
A 29-year-old pregnant woman who was asymptomatic and attending routine antenatal visits had a routine ultrasound examination in the 37 th week of pregnancy. Real-time ultrasonography revealed an irregular abdominal shape and an unclear margin mass, measuring 4.4 cm × 3.2 cm × 4 cm, located in the right lobe of the fetal liver. The mass had a mixed echogenicity (hyperechoic and or anechoic pattern) (Fig. 1A). Color doppler ultrasonography revealed punctuated blood flow in the mass and a short bar blood flow signal around the nodule (Fig. 1B).
Fetal MRI examination was performed on a 1.5T MRI scanner (SINGA™ Voyager, GE Health care) for further evaluation. MRI revealed a relatively clear well-circumscribed mass with mixed signals measuring 4.6 cm × 3.3 cm × 3.5 cm segments IVa and VIII of the liver. The lesion was of heterogeneous signal The Author confirms that the work described has not been published before (except in the form of an abstract or as part of lecture); that it is not under consideration for publication elsewhere; that its publication has been approved by all coauthors, if any; that its publication has been approved (tacitly or explicitly) by the responsible authorities at the institution where the work is carried out. The Author agrees to publication in Medicine. Medicine intensity, T1 hypointense (Fig. 1C), T2 hyperintense mixed with patchy hypointense (Fig. 1D), and with minimal diffusion restriction partially (Fig. 1E). The axial single-shot fast spinecho T2 weighted imaging (SSFSE T2WI) sequence revealed empty vascular around the mass and deformation of the inferior vena cava next to the mass (Fig. 1F). In summary, the lesion was diagnosed as hepatoblastoma.
The parents of fetus opted for pregnancy termination and agreed to an autopsy because of fear of a bad prognosis. Gross fetus samples showed hepatomegaly with a size of 12 cm × 8 cm × 4 cm ( Fig. 2A) and showed hemorrhage and necrosis after dissection (Fig. 2B). Routine histopathological examination ( Fig. 2C-F) displayed arteriovenous malformations in the liver and necrosis next to it. Hematoxylin and eosin staining images revealed small bile duct reactive hyperplasia around the hemorrhage and necrosis lesion, as well as cavernous hemangioma-like changes in the lesion margin. The final pathological diagnosis was hepatic arteriovenous malformation with hemorrhage and necrosis of surrounding tissues. The gene chip assay of tissue indicated no apparent abnormal findings (Fig. 3).

Discussion and conclusion
HAVMs are rare congenital lesions consisting of hepatic artery-portal vein fistula and hepatic artery-hepatic venous malformation. There have been only 8 reports of HAVMs in fetuses with typical imaging in ultrasonography in the previous literature, [3,4] but no MRI imaging data were provided. HAVMs are reported to be associated with HHT, which is inherited as an autosomal dominant disease caused by mutations in ENG, ACVRL1, or SMAD-4 genes. [5] HHT comprised a triad of epistaxis, telangiectasia, and suitable family history involving the mucocutaneous tissues, brain, lungs, and liver. [2,6] In our case, the fetus had no family history of inherited diseases through medical record review. Although the gene chip assay was normal in our case, whole-exome sequencing should be recommended because of insufficient deception. Mucosal bleeding points and vascular malformations of other organs had not been detected.
In HAVMs, abnormal blood circulation in the liver causes hepatomegaly and portal hypertension. [7] In our study, the fetus presented with significantly larger hepatomegaly than observed at the same gestational age. In adults, like other arteriovenous malformations, HAVMs show that arteries and veins communicate directly with high-pressure arteries feeding into low-pressure veins via malformed vascular structures without a capillary. [8] However, the blood supply of fetal liver, different from that of the adult, is dominantly supplied by the umbilical vein with a higher pressure than hepatic artery and vein. [6] Doppler ultrasonography plays a key role in detecting hemodynamic changes. Enhanced CT or MRI examinations are important for detecting arteriovenous malformations, including feeding arteries, intra-tumoral vasculature, and draining veins. Because of radiation protection and disabling of contrast agents for the fetus, indirect signs such as hemorrhage, necrosis mass, and disordered vessels around the lesion were detected instead of typical ultrasonography and MRI imaging signs. The imaging findings of this case are similar to the cerebral arteriovenous malformations that were finally diagnosed using DSA reported by Eguchi et al [9] High-pressure blood flow directly into vascular structures can disrupt the thin vessel with defects in smooth muscle and can ultimately cause hemorrhage. [10] The steal phenomenon caused by arteriovenous malformations leads to insufficient blood supply to other liver parts and causes necrosis. [11] In our case, ultrasound hypoechoic areas, T1WI hypointensity, and T2WI hyperintensity suggest old hemorrhagic necrosis, whereas ultrasound hyperechoic areas and T2WI patchy hypointensity suggest hemorrhage or hemosiderin deposition, consistent with gross specimens. The short bar blood flow signal around the nodule in color doppler ultrasonography and empty vascular around the mass on T2WI may suggest the presence of vascular malformations. Fetal liver lesions are rare, and differential diagnoses of hepatic arteriovenous malformations mainly include hepatic hemangioma, hepatoblastoma, and metastatic malignant tumors. Similar to our case, hepatoblastoma was predominantly T2-hyperintense and T1-hypointense with heterogeneity areas due to necrosis, hemorrhage, or calcification in MRI imaging. [12] However, hepatoblastoma was typically a hyperechoic solid mass with aggressive features such as rapid growth or metastases, which are helpful for differential diagnosis. [12,13] Diffusion restriction (high in diffusion-weighted imaging) may also contribute to misdiagnosis. Malignant tumors like hepatoblastoma have highly cellular tissue and several cell membranes  per unit volume, limiting water molecules diffusion into the extracellular space. [14] However, the diffusion restriction may indicate edematous areas of lesion or hemorrhage in the acute or subacute phase. [15] The deformation of inferior vena cava in T2-weighted imaging that was misidentified as an invasion of hepatoblastoma tumor was caused by compression of hemorrhage and necrosis. In addition to hemorrhage and necrosis, HAVMs can result in high-output heart failure. [16] In this case, cardiac abnormalities have not yet been described by ultrasonography. Additionally, multiple or large lesions of hepatic arteriovenous malformations can lead to significant complications, including hepatic encephalopathy, biliary ischemia, liver failure, and so on. [17] HAVM treatment mainly includes interventional treatment and surgical resection. Several molecular targeted drugs, such as the anti-VEGF inhibitor bevacizumab, are reported to improve the increased cardiac output due to HAVMs. [18,19] The best way is liver transplantation, [20] which increases the family's financial burden. preoperative diagnosis in our case seems to be very difficult because of the limitations of fetal ultrasonography and magnetic resonance imaging. The confirmed diagnosis of hepatic arteriovenous malformations in a fetus should rely on the common decision of imaging examinations, gross sample observation, and pathological examinations. Besides typical signs in imaging, sonographers and radiologists should improve the understanding of HAVMs and consider the possibility of tissue hemorrhage and necrosis caused by HAVMs when discovering liver disease during prenatal examinations.
preoperative diagnosis in our case seems to be very difficult because of the limitations of fetal ultrasonography and magnetic resonance imaging. The confirmed diagnosis of hepatic arteriovenous malformations in a fetus should rely on the common decision of imaging examinations, gross sample observation, and pathological examinations. Besides typical signs in imaging, sonographers and radiologists should improve the understanding of HAVMs and consider the possibility of tissue hemorrhage and necrosis caused by HAVMs when discovering liver disease during prenatal examinations.
It is common to misdiagnose HAVMs due to their nonspecific presentation. This case highlights the importance of having a high index of suspicion when diagnosing HAVMs.